Ulf Yrlid research group

Enteric infections resulting in diarrheal disease or typhoid fever remain a leading health problem in developing countries, causing 3 million deaths annually. New oral vaccines are hence of global importance. A successful oral vaccine must contain adjuvants, molecules that override the immune suppressive mechanisms that exist in the gut to avoid reactions against food proteins. The most potent oral adjuvants today are bacterial enterotoxins. The specific aim of this project is to investigate the interplay between these oral adjuvants, gut epithelium and gut dendritic cells. Dendritic cells are the key cells that direct the immune system due to their ability take up antigens and migrate to draining lymph nodes where they instruct the cells that confer immunity (lymphocytes).

We will use bone marrow chimeric techniques to determine the requirements for receptors and cellular interactions to generate immunity following oral vaccination. Novel surgical cannulation techniques to collect dendritic cells in lymph as they actually migrate from the intestine following oral vaccination will also be employed. To determine how commensal gut bacteria affect dendritic cell function, intestinal lymph dendritic cells will be collected from germ-free and conventional mice. Finally, we will identify the cells that contribute to a novel receptor mechanism involved in enterotoxin-induced diarrhea. The overall goal is to use these results to improve the design of novel oral vaccines.